One of the main determinants of the temperature at which C or A8 thermonociceptors are excited appears to be the rate at which the peripheral terminals of nociceptors are heated. The relationship between rate and threshold temperature is not simple however, and is likely modulated by other direct factors, such as duration of stimulation and surface area stimulated, as well as numerous indirect factors, including body, skin and air temperature, depth of the receptor in the skin, density of the skin, and specific characteristics of the heat source (thermode, normal radiant, various kinds of lasers). Perhaps the greatest advance in investigating these issues has been the development of standardized laser stimulation. However, there are great differences in the types of laser used, which can complicate comparisons between laboratories. We have chosen to investigate the use of a diode infrared laser, which should give optimal heating characteristics, in terms of direct heating of nociceptors in the skin, and which should inherently produce an extremely stable output. In addition, we will use a thermal camera to precisely measure temperature changes in the skin with an extremely precise temporal accuracy, so that the very rapid changes that can occur with lasers can be measured. Finally, we will combine these technologies with single unit peripheral nerve recordings in rats. In this way, we hope to determine optimal laser heating protocol for selective activation of either C or A5 thermonociceptors. Based on our preliminary work, as well as our examination of the literature, we hypothesize that very rapid rise times with this laser will allow for selective activation of A5 nociceptors, whereas lower rise time stimuli will selectively excite C nociceptors. Thus, we hope to show that temperatures of activation are not absolute, but rather are modulated by heating rate, duration, and size of area stimulated. We also intend to use the basic data gleaned from these studies to generate predictive modeling of temperature response functions at different depths of skin In this way, we hope, with this R21 early stage project, to develop a method which will allow future studies in terms of nociceptimetric testing in rats, examining the biomolecular mechanisms underlying selective nociceptor activation, and finally in the examination of central nervous system consequences, in humans, of specific activation of these different nociceptor types. [unreadable] [unreadable] [unreadable]